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Acetyl carnitine

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https://www.readbyqxmd.com/read/29668854/prostate-cancer-chemoprevention-by-sulforaphane-in-a-preclinical-mouse-model-is-associated-with-inhibition-of-fatty-acid-metabolism
#1
Krishna B Singh, Su-Hyeong Kim, Eun-Ryeong Hahm, Subrata K Pore, Bruce L Jacobs, Shivendra V Singh
Increased de novo synthesis of fatty acids is a rather unique and targetable mechanism of human prostate cancer. We have shown previously that oral administration of sulforaphane (SFN) significantly inhibits the incidence and/or burden of prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. The present study used cellular models of prostate cancer and archived plasma/adenocarcinoma tissues and sections from the TRAMP study to demonstrate inhibition of fatty acid synthesis by SFN treatment in vitro and in vivo...
April 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29659013/dietary-fat-and-fiber-interact-to-uniquely-modify-global-histone-post-translational-epigenetic-programming-in-a-rat-colon-cancer-progression-model
#2
Karen Triff, Mathew W McLean, Evelyn Callaway, Jennifer Goldsby, Ivan Ivanov, Robert S Chapkin
Dietary fermentable fiber generates short-chain fatty acids (SCFA), e.g., butyrate, in the colonic lumen which serves as a chemoprotective histone deacetylase inhibitor and/or as an acetylation substrate for histone acetylases. In addition, n-3 polyunsaturated fatty acids (n-3 PUFA) in fish oil can affect the chromatin landscape by acting as ligands for tumor suppressive nuclear receptors. In an effort to gain insight into the global dimension of post-translational modification of histones (including H3K4me3 and H3K9ac) and clarify the chemoprotective impact of dietary bioactive compounds on transcriptional control in a preclinical model of colon cancer, we generated high-resolution genome-wide RNA (RNA-Seq) and "chromatin-state" (H3K4me3-seq and H3K9ac-seq) maps for intestinal (epithelial colonocytes) crypts in rats treated with a colon carcinogen and fed diets containing bioactive (i) fish oil, (ii) fermentable fiber (a rich source of SCFA), (iii) a combination of fish oil plus pectin or (iv) control, devoid of fish oil or pectin...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29656010/age-related-defects-in-short-term-plasticity-are-reversed-by-acetyl-l-carnitine-at-the-mouse-calyx-of-held
#3
Mahendra Singh, Pedro Miura, Robert Renden
Hearing acuity and sound localization are affected by aging and may contribute to cognitive dementias. Although loss of sensorineural conduction is well documented to occur with age, little is known regarding short-term synaptic plasticity in central auditory nuclei. Age-related changes in synaptic transmission properties were evaluated at the mouse calyx of Held, a sign-inverting relay synapse in the circuit for sound localization, in juvenile adults (1 month old) and late middle-aged (18-21 months old) mice...
March 21, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29614331/carnitine-levels-and-mutations-in-the-slc22a5-gene-in-faroes-patients-with-parkinson-s-disease
#4
Súsanna Crooks, Sára Bech, Jónrit Halling, Debes H Christiansen, Beate Ritz, Maria Skaalum Petersen
INTRODUCTION: Mitochondrial dysfunction, oxidative stress and energy production have been implicated in the etiology of Parkinson's disease (PD). Several agents are under investigation for potential neuroprotective effects including acetyl-L-carnitine (ALC). OBJECTIVE: To investigate whether low carnitine levels and mutations in the SLC22A5 gene encoding the carnitine transporter are associates with Parkinson's disease (PD) risk in the Faroe Islands where the prevalence of both PD and carnitine transporter deficiency is high...
March 31, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29604498/oxidative-stress-and-mitochondrial-dysfunction-mediated-cd-induced-hepatic-lipid-accumulation-in-zebrafish-danio-rerio
#5
Ya-Xiong Pan, Zhi Luo, Mei-Qing Zhuo, Chuan-Chuan Wei, Guang-Hui Chen, Yu-Feng Song
The present study was performed to determine the effect of waterborne CdCl2 exposure influencing lipid deposition and metabolism, oxidative stress and mitochondrial dysfunction, and explore the underlying molecular mechanism of cadmium (Cd)-induced disorder of hepatic lipid metabolism in fish. To this end, adult zebrafish were exposed to three waterborne CdCl2 concentrations (0(control), 5 and 25 μg Cd/l, respectively) for 30 days. Lipid accumulation, the activities of enzymes related to lipid metabolism and oxidative stress, as well as the expression level of genes involved in lipid metabolism and mitophagy were determined in the liver of zebrafish...
March 17, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29588626/epistructured-catechins-egcg-and-ec-facilitate-apoptosis-induction-through-targeting-de-novo-lipogenesis-pathway-in-hepg2-cells
#6
Phuriwat Khiewkamrop, Pattamaphron Phunsomboon, Lysiane Richert, Dumrongsak Pekthong, Piyarat Srisawang
Background: Abnormally high expression of the mammalian de novo lipogenesis (DNL) pathway in various cancer cells promotes cell over-proliferation and resistance to apoptosis. Inhibition of key enzymes in the DNL pathway, namely, ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase (FASN) can increase apoptosis without cytotoxicity to non-cancerous cells, leading to the search for and presentation of novel selective and powerful targets for cancer therapy. Previous studies reported that epistructured catechins, epigallocatechin gallate (EGCG) and epicatechin (EC) exhibit different mechanisms regarding a strong inducer of apoptosis in various cancer cell lines...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29571766/dehydroepiandrosterone-reduces-accumulation-of-lipid-droplets-in-primary-chicken-hepatocytes-by-biotransformation-mediated-via-the-camp-pka-erk1-2-signaling-pathway
#7
Longlong Li, Chongyang Ge, Dian Wang, Lei Yu, Jinlong Zhao, Haitian Ma
Dehydroepiandrosterone (DHEA) is commonly used as a nutritional supplement to control fat deposition, but the mechanism of this action is poorly understood. In this study, we demonstrated that DHEA increased phosphorylation of AMP-activated protein kinase (p-AMPK). Elevated p-AMPK levels resulted in reduced expression of sterol regulatory element binding protein-1c, acetyl CoA carboxylase, fatty acid synthase and enhanced expression of peroxisome proliferators-activated receptor α and carnitine palmitoyl transferase-I, ultimately leading to the reduction of lipid droplet accumulation in primary chicken hepatocytes...
March 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29553847/reversal-of-high-fat-diet-induced-obesity-through-modulating-lipid-metabolic-enzymes-and-inflammatory-markers-expressions-in-rats
#8
Kalaivani A, V V Sathibabu Uddandrao, Brahmanaidu Parim, Saravanan Ganapathy, Nivedha P R, Sushma Chandulee Kancharla, Rameshreddy P, Swapna K, Vadivukkarasi Sasikumar
In this study, we evaluated the ameliorative potential of Cucurbita maxima seeds oil (CSO (100 mg/kg body weight)) supplementation to high fat diet (HFD)-induced obese rats for 30 days on the changes in body weight, markers of lipid metabolism such as LDL, HDL, triglycerides, total cholesterol, adiponectin, leptin, amylase, and lipase. We also investigated the effects of CSO on the changes of lipid metabolic enzymes such as fatty-acid synthase, acetyl CoA carboxylase, carnitine palmitoyl transferase-1, HMG CoA reductase, and inflammatory markers (TNF-α and IL-6)...
March 19, 2018: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29551309/mitochondrial-%C3%AE-oxidation-of-saturated-fatty-acids-in-humans
#9
REVIEW
María M Adeva-Andany, Natalia Carneiro-Freire, Mónica Seco-Filgueira, Carlos Fernández-Fernández, David Mouriño-Bayolo
Mitochondrial β-oxidation of fatty acids generates acetyl-coA, NADH and FADH2 . Acyl-coA synthetases catalyze the binding of fatty acids to coenzyme A to form fatty acyl-coA thioesters, the first step in the intracellular metabolism of fatty acids. l-carnitine system facilitates the transport of fatty acyl-coA esters across the mitochondrial membrane. Carnitine palmitoyltransferase-1 transfers acyl groups from coenzyme A to l-carnitine, forming acyl-carnitine esters at the outer mitochondrial membrane. Carnitine acyl-carnitine translocase exchanges acyl-carnitine esters that enter the mitochondria, by free l-carnitine...
March 15, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29549241/role-of-carnitine-and-its-derivatives-in-the-development-and-management-of-type-2-diabetes
#10
REVIEW
Judit Bene, Kinga Hadzsiev, Bela Melegh
Type 2 diabetes is a highly prevalent chronic metabolic disorder characterized by hyperglycemia and associated with several complications such as retinopathy, hyperlipidemia and polyneuropathy. The dysregulated fatty acid metabolism along with tissue lipid accumulation is generally assumed to be associated in the development of insulin resistance and T2D. Moreover, several studies suggest a central role for oxidative stress in the pathogenesis of the disease. Since L-carnitine (LC) has an indispensable role in lipid metabolism via its involvement in the β-oxidation of long-chain fatty acids and it has antioxidant properties as well, carnitine supplementation may prove to be an effective tool in the management of the clinical course of T2D...
March 7, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29546056/combination-of-mitochondrial-and-plasma-membrane-citrate-transporter-inhibitors-inhibits-de-novo-lipogenesis-pathway-and-triggers-apoptosis-in-hepatocellular-carcinoma-cells
#11
Wan-Angkan Poolsri, Phornpun Phokrai, Somrudee Suwankulanan, Narinthorn Phakdeeto, Pattamaphorn Phunsomboon, Dumrongsak Pekthong, Lysiane Richert, Sutatip Pongcharoen, Piyarat Srisawang
Increased expression levels of both mitochondrial citrate transporter (CTP) and plasma membrane citrate transporter (PMCT) proteins have been found in various cancers. The transported citrates by these two transporter proteins provide acetyl-CoA precursors for the de novo lipogenesis (DNL) pathway to support a high rate of cancer cell viability and development. Inhibition of the DNL pathway promotes cancer cell apoptosis without apparent cytotoxic to normal cells, leading to the representation of selective and powerful targets for cancer therapy...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29542003/scutellaria-baicalensis-regulates-ffa-metabolism-to-ameliorate-nafld-through-the-ampk-mediated-srebp-signaling-pathway
#12
Qian Chen, Mengyang Liu, Haiyang Yu, Jian Li, Sijian Wang, Yi Zhang, Feng Qiu, Tao Wang
Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-Ay mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA...
March 14, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29535221/organelle-derived-acetyl-coa-promotes-prostate-cancer-cell-survival-migration-and-metastasis-via-activation-of-calmodulin-kinase-ii
#13
Guoyu Yu, Chien-Jui Cheng, Song-Chang Lin, Yu-Chen Lee, Daniel E Frigo, Li-Yuan Yu-Lee, Gary E Gallick, Mark A Titus, Leta K Nutt, Sue-Hwa Lin
Although emerging evidence suggests a potential role of calcium/calmodulin-dependent kinase II (CaMKII) in prostate cancer (PCa), its role in PCa tumorigenesis is largely unknown. Here we examine whether the acetyl CoA-CaMKII pathway, first described in frog oocytes, promotes PCa tumorigenesis. In human PCa specimens, metastatic PCa expressed higher levels of active CaMKII compared to localized PCa. Correspondingly, basal CaMKII activity was significantly higher in the more tumorigenic PC3 and PC3-mm2 cells relative to the less tumorigenic LNCaP and C4-2B4 cells...
March 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29507904/improved-oxygenation-dramatically-alters-metabolism-and-gene-expression-in-cultured-primary-mouse-hepatocytes
#14
Eduardo H Gilglioni, Jung-Chin Chang, Suzanne Duijst, Simei Go, Aziza A A Adam, Ruurdtje Hoekstra, Arthur J Verhoeven, Emy L Ishii-Iwamoto, Ronald P J Oude Elferink
Primary hepatocyte culture is an important in vitro system for the study of liver functions. In vivo , hepatocytes have high oxidative metabolism. However, oxygen supply by means of diffusion in in vitro static cultures is much less than that by blood circulation in vivo . Therefore, we investigated whether hypoxia contributes to dedifferentiation and deregulated metabolism in cultured hepatocytes. To this end, murine hepatocytes were cultured under static or shaken (60 revolutions per minute) conditions in a collagen sandwich...
March 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29491466/characterization-of-exosomal-slc22a5-octn2-carnitine-transporter
#15
Lara Console, Mariafrancesca Scalise, Annamaria Tonazzi, Nicola Giangregorio, Cesare Indiveri
Exosomes are extracellular vesicles involved in cell-to-cell communication. Previous large scale proteomics revealed that they contain SLC proteins. However, no data on the function of exosomal SLCs is available, so far. An SLC localized in exosomes was here characterized for the first time: the carnitine transporter OCTN2 (SLC22A5). The protein was detected by Western Blot analysis in HEK293 exosomes. To investigate the functional properties of the exosomal OCTN2, the proteins extracted from vesicles were reconstituted into proteolipsomes and the transport function was measured as uptake of3 H-carnitine...
February 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29482657/fatty-acid-oxidation-promotes-reprogramming-by-enhancing-oxidative-phosphorylation-and-inhibiting-protein-kinase-c
#16
Zhaoyu Lin, Fei Liu, Peiliang Shi, Anying Song, Zan Huang, Dayuan Zou, Qin Chen, Jianxin Li, Xiang Gao
BACKGROUND: Changes in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in fatty acid oxidation, was significantly upregulated in the early stage of the reprogramming process...
February 26, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29466368/untargeted-metabolomics-reveals-distinct-metabolic-reprogramming-in-endothelial-cells-co-cultured-with-csc-and-non-csc-prostate-cancer-cell-subpopulations
#17
Anusha Jayaraman, Praveen Kumar, Silvia Marin, Pedro de Atauri, Francesca Mateo, Timothy M Thomson, Josep J Centelles, Stewart F Graham, Marta Cascante
Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study we aim to characterize the metabolic alterations in ECs influenced by the presence of tumour cells with extreme metastatic abilities. Human umbilical vein endothelial cells (HUVECs) were subjected to different microenvironmental conditions, such as the presence of highly metastatic PC-3M and highly invasive PC-3S prostate cancer cell lines, in addition to the angiogenic activator vascular endothelial growth factor (VEGF), under normoxia...
2018: PloS One
https://www.readbyqxmd.com/read/29459213/maximal-intensity-exercise-does-not-fully-restore-muscle-pyruvate-dehydrogenase-complex-activation-after-3-days-of-high-fat-dietary-intake
#18
D Constantin-Teodosiu, G Cederblad, M Bergström, P L Greenhaff
BACKGROUND & AIMS: Exercise activates muscle pyruvate dehydrogenase complex (PDC), but moderate intensity exercise fails to fully activate muscle PDC after high-fat diet [1]. We investigated whether maximal intensity exercise overcomes this inhibition. METHODS: Quadriceps femoris muscle biopsy samples were obtained from healthy males at rest, and after 46 and 92 electrically-evoked maximal intermittent isometric contractions, which were preceded by 3 days of either low- (18%) or high- (69%) isocaloric dietary fat intake (LFD and HFD, respectively)...
February 15, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29458450/transcriptomic-and-metabolomic-responses-induced-in-the-livers-of-growing-pigs-by-a-short-term-intravenous-infusion-of-sodium-butyrate
#19
E Ren, X Chen, S Yu, J Xu, Y Su, W Zhu
Previous studies showed that butyrate played benefit roles in the health and metabolism of animals. However, little information on the effects of butyrate on the metabolism of piglets at the extraintestinal level is available. The present study investigated transcriptomic and metabolomic responses in the livers of pigs to evaluate the effects of intravenous sodium butyrate (SB) on the body's metabolism at the extraintestinal level. A total of 12 Duroc×Landrace×Large White growing barrows (60 days of age) fitted with jugular vein cannula were randomly allocated to either the SB group or the control (CO) group...
February 20, 2018: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29454998/a-cell-death-assay-for-assessing-the-mitochondrial-targeting-of-proteins
#20
Daniel Camara Teixeira, Elizabeth L Cordonier, Subhashinee S K Wijeratne, Patricia Huebbe, Augusta Jamin, Sarah Jarecke, Matthew Wiebe, Janos Zempleni
The mitochondrial proteome comprises 1000 to 1500 proteins, in addition to proteins for which the mitochondrial localization is uncertain. About 800 diseases have been linked with mutations in mitochondrial proteins. We devised a cell survival assay for assessing the mitochondrial localization in a high-throughput format. This protocol allows us to assess the mitochondrial localization of proteins and their mutants, and to identify drugs and nutrients that modulate the mitochondrial targeting of proteins. The assay works equally well for proteins directed to the outer mitochondrial membrane, inner mitochondrial membrane mitochondrial and mitochondrial matrix, as demonstrated by assessing the mitochondrial targeting of the following proteins: carnitine palmitoyl transferase 1 (consensus sequence and R123C mutant), acetyl-CoA carboxylase 2, uncoupling protein 1 and holocarboxylase synthetase...
January 31, 2018: Journal of Nutritional Biochemistry
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